The high affinity IgE receptor (referred to below as FcεRI) expressed on the cell membrane of mast cells and basophils is known to be a key glycoprotein in the type I allergic reaction. When antigen-specific IgE's bonded to FcεRI are crosslinked by the corresponding polyvalent antigen (for example, cedar pollen antigen for individuals suffering from cedar pollen allergy, dust mite antigen for individuals suffering from dust mite allergies), the FcεRI's are clustered, the signal transduction mechanism operates, and the mast cells undergo initial activation. As a result, various chemical transmitters that evoke allergic inflammation, i.e., most prominently the histamine preliminarily stored in cell granules, are released and the new synthesis and release of leukotriene, prostaglandin, and so forth, which are intracellular metabolites, is explosively induced, evoking a type I allergic reaction.
In addition, cytokine secretion from mast cells is promoted by the clustering of FcεRI's on the mast cells, inducing the expression of various adhesion molecules in the neighboring vascular endothelial cells. Eosinophils and lymphocytes in the blood aggregate by binding via these adhesion molecules to the vascular endothelial cells at the site of inflammation. The late allergic reaction is evoked as a result. Moreover, the FcεRI expressed by the Langerhans cells of the skin is presumed to contribute to the pathogenesis of atopic dermatitis by antigen presentation and cytokine production.
Based on the preceding, a promising strategy for the development of agents for allergy prophylaxis treatment is to target the FcεRI that specifically mediates type I allergy and thereby block signal transduction from this receptor at the point of origin.
FcεRI is also known to participate in platelet activation and glomerulonephritis, and given this it is also promising to carry out the development of thrombosis and glomerulonephiritis by targeting FcεRI.
In humans, human FcεRI functions expressed on the cell surface as a tetramer of an α-chain, a β-chain, and 2 γ-chains or as a trimer of an α-chain and 2 γ-chains. The extracellular region of the α-chain binds-directly to IgE while the β-chain γ-chain participate in signal transduction into the cell. The γ-chain assembles with the other molecules, which have a ligand binding site, to form a receptor on the cell surface. When ligand binds to the receptor's ligand binding site, the γ-chain transduces the signal into the cell.
For example, the γ-chain has been reported to perform the function of transmitting an activation signal into the cell in the FcεRI-mediated induction of allergic reactions (refer, for example, to Non-Patent documents 1 to 3). In addition, the γ-chain has been reported to induce the platelet activation reaction by associating with the collagen receptor GP VI on the platelet (refer, for example, to Non-Patent document 4).
The γ-chain is also a constituent element of the IgG receptors FcγRIII and FcγRI and the IgA receptor FcαR, and the suggestion has also been made these FcR's participate in glomerulonephritis-(refer, for example, to Non-Patent document 5).    Non-Patent document 1 Ra C et al., Nature, 341:752-754 (1989);    Non-Patent document 2 Blank U et al., Nature, 337; 187-189 (1989);    Non-Patent document 3 Kinet J P, Annual Review of Immunology, 17:931-972 (1999);    Non-Patent document 4 Konishi H et al., Circulation, 105(8):912-916 (2002);    Non-Patent document 5 Suzuki Y et al., Kidney Int., 54(4):1166-1174 (1998)
However, on the subject of transcriptional regulatory regions for the high affinity human IgE receptor γ-chain, only the analysis by Brini A T et al., in 1993 has been carried out, and to date no detailed analysis that precisely identifies transcriptional regulatory elements and/or transcriptional regulatory factors has been performed.
As a result of intensive investigations, the present inventors succeeded in identifying, from within previously unanalyzed regions, regions that participate in the transcriptional regulation of the human FcεRI γ-chain gene and in identifying transcription factors that bind to these regions and were thereby able to achieve the present invention.